A new platform to test the effectiveness of anti-cancer drugs

This is a question that Professor Gopal Iyer, Head of the Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore (NCCS), has been trying to answer throughout his career as a clinician-scientist.

Now, through a research collaboration with Assistant Professor Eliza Fong, from the Department of Biomedical Engineering at the NUS College of Design and Engineering, Prof Iyer may have the answer.

Tumours are highly complex tissues made up of not just cancer cells, but a variety of supporting cells. The composition of these different cell types within each tumour can vary widely, explaining why two patients with the same cancer may respond differently to the same therapy.  

Whether a treatment is effective for a specific patient is not guaranteed. Unless they undergo complex and expensive testing, it can sometimes take around six months after a patient has started treatment to find out if a treatment is working for them.  

Prof Iyer, who is also Head of the Division of Medical Sciences, the translational research arm of NCCS, has studied this in his research lab but till now has not been able to find a solution.

 

When Prof Iyer and Asst Prof Fong started collaborating, they decided to approach the problem differently, tapping on Asst Prof Fong’s expertise as an engineer.

“Cancer cells are protected and supported by other pieces or cell types present in the tumour. Many drugs now target these supporting cells to eliminate cancer cells”, explained Asst Prof Fong.

With that in mind, the research team decided to construct a bioengineered platform that is able to preserve the tumour and all its supporting cells.

Once the platform was developed, the team tested it. Using slices of tumours that had been removed from patients with head and neck cancer, they found that tumour fragments cultured in the platform were better preserved compared to when standard methods were used. They also discovered that tumour fragments could be kept alive for up to 10 days, a significant 8 days longer than when using standard methods. This indicated that more thorough drug testing and screening would be possible. 

The team then conducted advanced single-cell analysis at NCCS, which demonstrated that the various components in the original tumour were also present in the cultured tumour fragments. This allows tumours being preserved in the hydrogel, known as ‘patient avatars’, to better demonstrate the effects of drugs on cancer cells. 

Excitingly, the study also showed that the ‘patient avatars’ for head and neck cancer patients could be used to accurately predict the drug response to immune checkpoint inhibitors, a type of immunotherapy. This showed the platform’s potential to help clinicians select patients who should receive immune checkpoint inhibitors as it would work best for them. In turn, this reduces the possibility of giving the drug to patients less likely to respond to treatment, potentially saving time and cost. 

 

The findings from this study have important implications for cancer treatment in the future. By studying the response of individual tumours to specific treatments, clinician-scientists and researchers can identify biomarkers and group patients with similar characteristics so that their treatment outcomes can be improved.

“This platform allows us to test drugs in a more realistic setting with the goal of improving their efficacy. With this, we hope to alleviate some of the uncertainty and anxiety that can be a part of a patient’s experience when they undergo cancer treatment,” said Prof Iyer.

The team hopes to demonstrate the viability of the platform across cancer types and is planning to take the bioengineered hydrogel to a larger-scale clinical trial. They also hope to build a local repository of tumours for Singapore and the region that can be used for more comprehensive drug testing and pre-screening. 

The results of the study were published in the journal Biomaterials on 20 January 2024.